Autoradiographic visualization of nicotine receptors labeled with either 3H-nicotine or 3H-acetylcholine in the presence of atropine revealed high concentrations in the specific thalamic nuclei, interpeduncular nucleus, superior colliculus, substantia nigra, molecular layer of the dentate gyrus, presubiculum and laminae III/IV of the cerebral cortex. Labeling of nicotine receptors with alpha-bungarotoxin revealed an entirely different pattern. Binding was highest in the cerebral cortex, hypothalamus, hippocampus, inferior colliculus and in certain brainstem nuclei, suggesting the presence in brain of two distinct subtypes of the nicotine receptor. Lesions of the habenula decreased the binding of 3H-nicotine in the interpeduncular nucleus. Lesions of the medial forebrain bundle decreased the binding of 3H-nicotine in the zona compacta of the substantia nigra suggesting the presence of nicotine receptors on dopamine cell bodies. Systemic injections of nicotine increased the firing rate of dopaminergic zona compacta neurons in the substantia nigra suggesting that nicotine can influence dopaminergic neural activity. Injections of phencyclidine (PCP) into the nucleus accumbens produced locomotor excitation which was blocked by systemic administration of haloperidol. Injections of PCP into periaqueductal gray matter and mesencephalic reticular formation produced decreases in locomotor output. Calcitonin produced patent analgesic effects following injections into the periaqueductal gray matter and reticular formation. Electrical stimulation of the arcute nucleus produced a naloxone reversible analgesic effect accompanied by decreases in binding of 3H-diprenorphine in the terminal regions of the endorphin system suggesting the release of endorphins by this manipulation. Employing local cerebral glucose utilization (LCGU) procedures, rewarding brain stimulation of the ventral tegmental area and the substantia nigra divergent and covergent patterns of metabolic activation were observed.